Clinical and epidemiological characteristics and outcomes of Coronavirus disease-19 patients in a large longitudinal study.

OBJECTIVE: This study aimed to determine the clinical and epidemiological characteristics and outcomes of Coronavirus disease (COVID)-19 patients. METHODS: In this large cohort study, 15,409 confirmed patients with the COVID-19 of different severities were followed-up from three specialized COVID-19 hospitals between March 18 and October 11, 2020 in Iraqi Kurdistan. The predictors of mortality and severity were examined in binary logistic regression analysis. RESULTS: The incidence rate of severe/critical status was 12.3% with a median age of 36.0 and case fatality rate (CFR) of 1.98%. The incidence rate of severe/critical conditions and CFR rose with increased age groups; except for 0-14 years (11.9%). The incidence rate of severe/critical patients and CFR was 8.3% and 0.5%, 21.1% and 4.0%, and 23.7% and 8.7% in 15-49 years, 50-64 years, and 65 and older age groups, respectively. The severity of the disease and CFR was associated with coexisting chronic diseases such as cardiovascular diseases (18.2% and 3.1%) and diabetes mellitus (19.8% and 3.4%). The asymptomatic patients (8400 and 54.5%) had statistically higher CFR; 2.3% versus 1.6% (P = 0.006). The most common symptoms on diagnosis were fever (31.9%), cough (23.5%), loss of smell/taste (16.3%), sore throat (15.7%), shortness of breath (9.8%), and headache (9.5%). The results showed that being older was the only predictor of mortality and severity in COVID-19 patients. CONCLUSIONS: This region has a low incidence of severe-critic status and CFR. The patients with coexisting medical conditions are more likely to have severe conditions and die of COVID-19. The older age predicts severe/critic status and higher CFR.

A 5-year experience characterizing the demographic and clinical profile and directly observed treatment short-course treatment outcome in National Tuberculosis Center of Duhok province, Iraqi Kurdistan.

BACKGROUND: The objectives were to describe the demographic and clinical profile and treatment outcomes in the National Tuberculosis Program Center of Duhok governorate. METHODS: This was a descriptive retrospective study of all forms of drug-susceptible tuberculosis cases in the National Tuberculosis Program Center of Duhok. The Electronic Nominal Recording Reporting System data of tuberculosis cases were reviewed during 2014-2018. Information on the demographic, clinical, and laboratory characteristics of the patients were analyzed. Tuberculosis trends and treatment outcomes were determined. RESULTS: A total of 1063 tuberculosis patients visited the National Tuberculosis Program Center, of whom 905 were from Duhok. The estimated tuberculosis notification rate per 100,000 people in Duhok governorate was 14.06, 16.16, 10.43, 11.05, and 10.34 for the years 2014, 2015, 2016, 2017, and 2018, respectively. The most affected age group was 15-24 years. The male cases were predominant. Most patients (97.3%) were native Iraqi. There were 718 (67.5%) pulmonary tuberculosis cases and 345 (32.5%) extra-pulmonary tuberculosis cases; tuberculosis lymphadenitis was the most common presentation. The majority of extra-pulmonary tuberculosis patients were females aged 15-24 years (p = 0.019), and patients aged ⩾65 years were associated with pulmonary tuberculosis and extra-pulmonary tuberculosis in males (p ⩽ 0.001). The highest tuberculosis incidence occurred in winter (288 patients). The patient treatment outcomes were as follows: 90.7% successful treatment, 1.6% lost to follow-up, 6.7% death, 0.3 transferred out, and 0.8 treatment failure. CONCLUSION: There was a high frequency of extra-pulmonary tuberculosis, which may reflect overestimation in its diagnosis. Therefore, meticulous evaluations should be provided. The treatment outcome was satisfactory in the center. Hence, we should maintain the favorable work to attain tuberculosis control objectives. Performing GeneXpert for all tuberculosis cases and introducing culture and drug susceptibility testing should be an urgent plan to strengthen the diagnosis of susceptible and drug-resistant tuberculosis cases.

First insight into latent tuberculosis infection among household contacts of tuberculosis patients in Duhok, Iraqi Kurdistan: using tuberculin skin test and QuantiFERON-TB Gold Plus test.

BACKGROUND: The objectives were to estimate the prevalence of latent tuberculosis infection (LTBI) among household contacts (HHCs) with active TB patients, and to identify their risk factors. METHODS: A prospective, cross sectional study was conducted from May to October 2018. All HHCs with active TB cases were included. The subjects underwent two tests: Quantiferon TB-Gold plus assay (QFT-Plus) and tuberculin skin test (TST). Data were analyzed using the Statistical Package for Social Sciences 25. RESULTS: Among 521 HHCs, 101 (24.05%) revealed positive TST and 80 (19.85%) positive QFT-Plus. The significant risk factors associated with positive TST individuals were ≥ 15 years, immunosuppressive therapy, and pulmonary TB (PTB) patients; whereas, those with QFT-Plus positive were ≥ 45 years, alcohol consumption, and immunosuppressive therapy. The concordance rate among 309 individuals who performed both tests was 0.88 %; the kappa value showed good agreement (k = 0.679) and significant correlation (P < 0.001). CONCLUSIONS: The overall rate of LTBI was intermediate. Screening of LTBI should be routine among HHCs, regardless of the site of the disease. Age ≥ 15 years, alcoholics, immunosuppressive therapy, and PTB were potential risk factors. There was a good concordance between TST and QFT-Plus. A QFT-Plus can overcome the limitation of a BCG vaccinated individual, especially in early life.

Latent Tuberculosis Infection among Healthcare Workers in Duhok Province: From Screening to Prophylactic Treatment.

Healthcare workers (HCWs) are at increased risk of infection with Mycobacterium tuberculosis (Mtb) and, hence, of developing tuberculosis (TB) disease. The aims of this study are to identify the prevalence and determinants of latent TB infection (LTBI) among HCWs in Duhok Province. This is a cross-sectional prospective study conducted during April-July 2018 in different health care facilities of Duhok province. HCWs at multiple levels were selected by a non-systematic random sampling method. Information on demographic and associated risk factors of LTBI were collected by using a standardized questionnaire. Thereafter, all HCWs underwent QuantiFERON Gold Plus (QFT-Plus) assay. HCWs with indeterminate QFT-Plus underwent a Tuberculin Skin Test. HCWs with positive results were further evaluated by smear microscopy investigation and chest X-ray examination. Three hundred ninety-five HCWs were enrolled; 49 (12%) tested positive for LTBI. The mean age of the HCWs was 33.4 ± 9.25 with a female predominance (51.1%). According to the univariate analysis, LTBI was significantly higher among HCWs with the following: age groups ≥ 30 years, alcohol intake, ≥ 11 years of employment, high risk stratification workplaces, and medical doctors. In the multivariate analysis, the age group of 30-39 years (OR = 0.288, 95% CI: 0.105-0.794, p value = 0.016) was the only risk factor associated with LTBI. Further medical investigations did not reveal active TB cases among HCWs with LTBI. With regards to prophylactic treatment, 31 (63.3%) LTBI HCWs accepted the treatment, whereas 18 (36.7%) declined the chemoprophylaxis. Of these 31 HCWs on chemoprophylaxis, 12 (38.7%) received isoniazid (INH) for six months, 17 (54.8%) received INH in combination with rifampicin (RMP) for three months, and two (6.5%) received alternative therapy because of anti-TB drug intolerance. In conclusions, although Iraq is a relatively high TB burden country, the prevalence of LTBI among Duhok HCWs is relatively low. It is important to screen HCWs in Duhok for LTBI, particularly medical doctors, young adults, alcoholics, and those whom had a long duration of employment in high-risk workplaces. The acceptance rate of HCWs with LTBI to chemoprophylaxis was low. Therefore, ensuring medical efforts to educate the healthcare staff particularly, non-professionals are a priority to encourage chemoprophylaxis acceptance.

Drug resistance-related mutations in multidrug-resistant Mycobacterium tuberculosis isolates from diverse geographical regions.

BACKGROUND: Drug resistance in Mycobacterium tuberculosis is associated with chromosomal mutations in selected genes. These mutations can be screened for an early warning system for drug-resistant tuberculosis. The prevalence of individual mutations differs geographically, which must be considered in developing globally applicable screening tests. METHODS: In order to analyse the geographical distribution and frequency of mutations conferring resistance to rifampicin, isoniazid and fluoroquinolones, the researchers investigated the presence of mutations in the rpoB gene, the katG gene, the mabA-inhA promoter region and the gyrA gene in clinical isolates of multidrug-resistant tuberculosis (MDR-TB) from Belarus, China, Iran/Iraq, Honduras, Romania and Uganda. For each study site, the researchers described the distribution of specific mutations in 20 clinical MDR-isolates. RESULTS: The distribution of resistance-related mutations varied significantly between the study sites. Settings with a high incidence of MDR-TB, such as Belarus, showed a narrower spectrum of mutations related to rifampicin and isoniazid resistance and also a higher prevalence of fluoroquinolone resistance than study sites with a lower MDR-TB prevalence. CONCLUSION: This study confirms that there are significant geographical differences in the distribution of resistance-related mutations and suggests that an increased understanding of such differences in the specific distribution of resistance conferring mutations is crucial for development of new, generally applicable, molecular tools for rapid diagnosis of drug-resistant TB. The fact that a narrower distribution of mutations in high MDR-TB prevalence settings was seen suggests that much of the problems in these settings can be a result of an ongoing transmission of certain MDR-TB strains.

Sequential adaptation in latent tuberculosis bacilli: observation by atomic force microscopy (AFM).

Mycobacterium tuberculosis (MTB) can persist within the human host for years without causing disease, in a syndrome known as latent tuberculosis. The mechanisms by which M. tuberculosis establishes a latent metabolic state is unknown, but it is hypothesized that reduced oxygen tension may trigger the bacillus to enter a state of latency. Therefore, we are studying anaerobic culture of M. tuberculosis (H37RV) as a model of latency. For the first time, the sequential adaptation of latent bacilli (every 90 days for 48 months) viewed under Atomic Force Microscopy (AFM). Two types of adaptation were observed and are described here. First, cells are undergoing temporary adaptation (from 1 to 18 months of latency) that includes; thickening of cell wall (20.5±1.8 nm versus 15.2±1.8 nm, P<0.05), formation of ovoid cells by "folding phenomena"(65-70%), size reduction (0.8±0.1 µm versus 2.5±0.5 µm), and budding type of cell division (20-25%).A second feature include changes that accompany development of specialized cells i.e., production of spore like cells (0.5±0.2 µm) and their progeny (filterable non -acid fast forms; 150 to 300 µm in size). Although, these cells were not real spore because they fail to form a heat resistant colony forming units, after incubation for 35-40 min at 65°C. The filterable non-acid fast forms of bacilli are metabolically active and increased their number by symmetrical type of cell-division. Therefore, survival strategies that developed by M. tuberculosis under oxygen limited condition are linked to its shape, size and conspicuous loss of acid fastness.

Anti-tuberculosis drug resistance and associated risk factors in a tertiary level TB center in Iran: a retrospective analysis.

INTRODUCTION: This study aimed to determine first-line anti-tuberculosis drug resistance rates in new and previously treated cases and to identify risk factors associated with multidrug resistant tuberculosis (MDR-TB) at the National Reference Tuberculosis Laboratory of Iran. METHODOLOGY: This was a retrospective analysis of all confirmed TB patients from December 2000 to June 2005. Drug susceptibility testing to isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide was performed on Löwenstein-Jensen (LJ) medium according to the proportion method. RESULTS: Mycobacterium tuberculosis strains were isolated from 1,742 patients with TB, of whom 935 (53.7%) were male. The mean age of patients was 44.2 ± 17.4 years (SD). A total of 1,074 patients were native Iranians while 668 (38.3%) were immigrant patients. Out of 1,139 (65.4%) new cases, 340 (29.9%) had at least one drug resistance. Of 603 (34.6%) previously treated cases, 416 (69.0%) had resistant strains. There were 263 patients (15.1%) with MDR-TB, 72 of whom were new (6.3% of all new cases) and 191 were previously treated (31.7% of all previously treated cases). Factors associated with MDR-TB included age under 45 years, male sex, previous TB treatment, immigration, poor living conditions, and unemployment. CONCLUSIONS: The high rate of initial resistance in MDR-TB cases and the high rate of MDR-TB in a young age group were indicators of recent transmission. Therefore, closer monitoring of transmission trends of drug resistant strains should be considered as priority, to ensure a successful TB control programme.

Growth and cell-division in extensive (XDR) and extremely drug resistant (XXDR) tuberculosis strains: transmission and atomic force observation.

The ultra-structure of Mycobacterium tuberculosis (MTB) was examined by transmission electronic (TEM)) and atomic force microscopy (AFM). The study was performed to describe the morphology of susceptible, multidrug-resistant (MDR), extensively drug-resistant (XDR) and extremely drug-resistant tuberculosis isolates (XXDR-TB) during their exponential growth phase. Four types of cell division were observed and described. While three of them (symmetrical, asymmetrical and branching type) occurred in all isolates studied, the fourth one (adapted type) was seen only in XDR and XXDR-TB bacilli. In the fourth type of cell division, a rod shaped mother cell produced a small round shape bacillus (0.3-0.5 µm). These round cells were different from buds or polar division, but similar to terminal endospores without showing the typing heat resistance. Based on the present observation, we suggest that XDR-and XXDR-TB bacilli accommodate changes helping them to overcome the hostile environment. Viewed under AFM, the other frequently detected shapes in MTB isolates were oval, V, Y and multi-branching filaments. These shape variation confirmed pleomorphic phenomena in MTB populations and the specific features of pan-resistant strains.

Active pulmonary tuberculosis manifesting with idiopathic thrombocytopenic purpura: a rare presentation.

A 17-year-old girl presented with a 3-day history of epistaxis, vaginal bleeding and petechiae over the lower extremities. The patient had been feeling unwell with productive cough, fever, chills, poor appetite and weight loss for 2 months. Laboratory findings revealed anemia and thrombocytopenia, whereas bone marrow examination was unremarkable. She was diagnosed as having idiopathic thrombocytopenic purpura (ITP) in association with active tuberculosis (TB). The patient was treated with intravenous immunoglobulin (IVIg) and corticosteroid along with anti-TB drugs. During the follow-up period there was no recurrence of thrombocytopenia or TB. It is important to consider TB in the differential diagnosis of ITP, particularly in high TB-burden areas.